Effects of F-180, a new selective vasoconstrictor peptide, compared with terlipressin and vasopressin on systemic and splanchnic hemodynamics in a rat model of portal hypertension.
The present study is aimed at characterizing the portal, splanchnic, and systemic circulatory effects of F-180, a new long-acting analog of vasopressin (VP) with selective effect on the vascular (V1) receptor, both in normal rats and in portal-hypertensive animals. In preliminary vasopressor tests, F-180 was 18 times more potent than terlipressin (TP) (164 +/- 10 IU x mmol(-1) vs. 9.2 +/- 1.2 IU x mmol(-1)) and four times less potent than arginine VP (614 +/- 25 IU x mmol(-1)). F-180 had negligible antidiuretic potency, resulting in vascular selectivity (V1/V2) of 858 compared with 1.0 for VP and 2.2 for TP. In portal-hypertensive rats with partial portal vein ligation (PPVL), the vasopressor effect of F-180 was 19 times that of TP on a molar basis (ED50 F-180: 0.54 vs. TP: 10.02 nmol x kg(-1)). At low doses (0.405 nmol x kg(-1)), F-180 significantly reduced portal pressure (PP) (-13.8% +/- 6.7%) and superior mesenteric artery blood flow (SMABF) (-25.6% +/- 4.5%), whereas TP at 8.10 nmol x kg(-1) was required to achieve comparable splanchnic effects; however, this dose caused a significantly greater increase in mean arterial pressure (MAP) than F-180 at 0.405 nmol x kg(-1) (28.2% +/- 2.7% vs. 8.9% +/- 2.7% at 20 minutes; P < .05). F-180 at 0.405 nmol x kg(-1) had effects on PP and SMABF similar to a 30-minute intravenous infusion of VP at 10 mU x kg(-1) in PPVL rats, but VP caused a significantly greater elevation in systemic vascular resistance (SVR) and MAP, and more pronounced reduction in cardiac index (P < .05).
Bernadich
C
C
Hepatic Hemodynamic Laboratory, Hospital Clinic i Provincial, University of Barcelona, Catalunya, Spain.
Bandi
J C
JC
Melin
P
P
Bosch
J
J
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004231:Diuresis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006975:Hypertension, Portal / Q000503:physiopathology*; D008236:Lypressin / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D017538:Mesenteric Artery, Superior / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D013152:Splanchnic Circulation / Q000187:drug effects*; D000077585:Terlipressin; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014667:Vasopressins / Q000494:pharmacology*
D000959:Antihypertensive Agents; C110660:F-180 vasoconstrictor peptide; D014662:Vasoconstrictor Agents; D014667:Vasopressins; D008236:Lypressin; D000077585:Terlipressin